The toxicity of chemical agents which may be hazardous to human health and to other species is being studied in mammaliam cells cultured in vitro to gain an insight into the molecular mechanisms of toxicity. The toxicity of selected organochlorine agents has been demonstrated. The most striking effect of these agents on cell metabolism is concerned with phospholipid metabolism. In the mouse L5178Y lymphoma cell line, DDT, DDT analogs, and 4-chlorobiphenyl stimulate the rate of de novo synthesis of phosphatidylcholine. There is a positive correlation between the relative toxicity of organochlorine agents and their ability to stimulate phosphatidylcholine (PC) synthesis. The effect of organochlorine agents on phospholipid metabolism varies with the cell line studied. Phosphatidylcholine in the mouse Balb C/3T3 fibroblast cell line was the least effected, while stimulation of the rate of PC synthesis was highest in human embryonic (WI-38) lung fibroblasts. The effect of organochlorine agents on PC synthesis in WI-38 cells is similar to that elicited by the tumor promotor, tetradecanoylphorbol acetate.